Factory Default Settings Research Articles

Tailoring to Search Engines: Bottom-Up Proteomics with Collision Energies Optimized for Identification Confidence.

Bottom-up proteomics relies on identification of peptides from tandem mass spectra, usually via matching against sequence databases. Confidence in a peptide–spectrum match can be characterized by a score value given by the database search engines, and it depends on the information content and the quality of the spectrum. The latter are influenced by experimental parameters, of which the collision energy is the most important one in the case of collision-induced dissociation. We examined how the identification score of the Byonic and Andromeda (MaxQuant) engines varies with collision energy for more than a thousand individual peptides from a HeLa tryptic digest on a QTof instrument. We thereby extended our earlier study on Mascot scores and corroborated its findings on the potential bimodal nature of this energy dependence. Optimal energies as a function of m/z show comparable linear trends for the three engines. On the basis of peptide-level results, we designed methods with one or two liquid chromatography–tandem mass spectrometry (LC-MS/MS) runs and various collision energy settings and assessed their practical performance in peptide and protein identification from the HeLa standard sample. A 10–40% gain in various measures, such as the number of identified proteins or sequence coverage, was obtained over the factory default settings. Best performing methods differ for the three engines, suggesting that the experimental parameters should be fine-tuned to the choice of the engine. We also recommend a simple approach and provide reference data to ease the transfer of the optimized methods to other mass spectrometers relevant for proteomics. We demonstrate the utility of this approach on an Orbitrap instrument. Data sets can be accessed via the MassIVE repository (MSV000086379).

Abstract 299: Effect of Start Position and Compression Depth on Mechanical CPR Hemodynamics in Swine

Introduction: Mechanical devices offer the ability to provide consistent fixed-depth chest compressions during CPR. Although compression depth is considered a primary determinant of CPR quality, the influence of other device settings has received less attention. Accordingly, we evaluated the combined effect of compression depth and device start position on CPR hemodynamics in a porcine model of cardiac arrest (CA). Methods: Swine (n=119) were subjected to 7-10 min of CA following electrical induction of ventricular fibrillation. CPR was subsequently performed manually (target peak aortic pressure: 100 mmHg; n=73) or with a mechanical compression system (LUCAS 3.1, Stryker; n=46). Within the mechanical CPR group, animals received 102 compressions/min using either factory default settings (“QuickFit” automated suction cup start position; compression depth: 2.1”; n=13) or custom settings (manual suction cup start position; compression depth: 1.8”; n=33). Aortic pressure (Ao), coronary perfusion pressure (CPP), and regional cerebral oxygen saturation (rSO 2 ; via near infrared spectroscopy) were compared between groups after 1 min of CPR. Results: Mechanical CPR with automated suction cup start position and compression depth of 2.1” resulted in significantly higher peak Ao and CPP than mechanical CPR with manual start position and compression depth of 1.8” ( Table ). Compared with manual CPR, only mechanical CPR with automated start position and compression depth of 2.1” led to a higher CPP. However, cerebral rSO 2 values fell from 61±1 % at baseline to 49±1 % during CA (p<0.01) and did not increase during CPR in any group. Conclusion: Compared with a manual start position and compression depth of 1.8”, use of the LUCAS “QuickFit” feature and compression depth of 2.1” led to a significantly higher CPP during mechanical CPR. Future studies are necessary to determine if differences persist during prolonged CPR with and without concomitant vasopressor administration.

Development and Validation of Waste Decontamination Cycle in a Biosafety Level 3 Laboratory.

Steam sterilization has been used for decades to effectively kill microbial contaminants in a variety of medical and commercial settings. One of the most critical aspects of safe operations in biosafety level 3 biocontainment laboratories (BSL-3) is the effective inactivation of biological select agents in the waste generated in these environments. The Instituto Nacional de Enfermedades Virales Humanas "Dr. Julio I. Maiztegui" (INEVH, Pergamino, Argentina) is an institute that offers epidemiological surveillance, production of biological reagents, and production of biologicals for human use and studies of reservoirs and vectors. Some of the activities need to be done in a BSL-3 that provides biocontainment, ensuring that the materials are decontaminated before they leave the facility. The objective of this study was to design and validate a decontamination procedure for biological waste from the BSL-3 facility that guarantees steam sterilization processes. The amount and the distribution of biological waste into the autoclave and other physical parameters were defined and evaluated by calculating lethalities. We evaluated autoclave basic factory programmed cycles, and it was concluded that the sterilization autoclave cycle was not efficient for decontamination of waste. A new simulated load distribution had to be defined. The results demonstrated that autoclave factory default settings can be inadequate for sterilizing highly infectious waste, depending of types of waste, such as animal carcass and animal bed waste. These results of the validation process can set the standard to the design of waste management protocols to ensure effective treatment of highly infectious biological waste.

Adjustment of the data acquisition window for the assessment of sensorimotor gating mechanisms in rodents

The acoustic startle reflex (ASR) is a short and intense defensive reaction in response to a loud and unexpected acoustic stimulus. The ASR can be modulated through sensorimotor gating processes, such as prepulse inhibition (PPI), a neurological phenomenon in which a weak pre-stimulus inhibits the reaction to a startling stimulus. The reduction of the amplitude of ASR reflects the ability of the CNS to adapt to a salient sensory stimulus when a preceding weaker signal is perceived. Despite its obvious importance for translational research studies, when the data acquisition window is not properly configured, the measurement of ASR may contain artifacts or be incorrect altogether. In this paper, we issue our recommendations for the correct definition of the response window to achieve good-quality ASR/PPI measurements in order to standardize and implement the method across conditions.•Parameters for detection of peak responses need to be carefully configured, otherwise the risk of obtaining unwanted artifacts or high signal-to-noise ratio increases considerably.•Custom settings yield traces with tighter baseline, higher amplitude, and shorter latency compared to factory default settings.•FFT heatmaps show a solid color-correlation when using custom settings, without the appearance of artifacts.

Thermal infrared imaging of conifer leaf temperatures: Comparison to thermocouple measurements and assessment of environmental influences

Thermal infrared (TIR) imaging provides a potentially powerful tool for ecological and biometeorological research, but the accuracy of TIR imaging of plant surface temperature in a variable outdoor environment has been poorly characterized. This study evaluated the accuracy of TIR measurements of a conifer tree that were made using the thermal camera’s factory default settings, and developed a post-collection data processing method to correct measurements for ambient conditions that depart from the factory default settings. We conducted a 42-day measurement campaign in Corvallis, Oregon during spring 2014 that focused on the canopy temperature of a noble fir (Abies procera) and included the simultaneous collection of meteorological data and leaf temperature measurements with an array of thermocouples. We then developed empirical functions for temperature corrections that better accounted for emissivity, and atmospheric and reflected temperature. The original TIR temperatures using the factory settings averaged 8.6±5.6°C (−4.2 to 25.4°C in range), and the original TIR temperatures differed from the thermocouple temperatures by 1.4–1.6K. The TIR temperatures were generally accurate, except for a low temperature bias at leaf temperatures below 5°C. TIR temperature corrections reduced this bias to a <1.0K mean error relative to the thermocouples. Our results show that TIR measurements can be corrected to more accurately quantify canopy temperature, and that the importance of this correction increases under more extreme ambient conditions, such as colder periods.

Validation of Autoclave Protocols for Successful Decontamination of Category A Medical Waste Generated from Care of Patients with Serious Communicable Diseases.

In response to the Ebola outbreak in 2014, many hospitals designated specific areas to care for patients with Ebola and other highly infectious diseases. The safe handling of category A infectious substances is a unique challenge in this environment. One solution is on-site waste treatment with a steam sterilizer or autoclave. The Johns Hopkins Hospital (JHH) installed two pass-through autoclaves in its biocontainment unit (BCU). The JHH BCU and The Johns Hopkins biosafety level 3 (BSL-3) clinical microbiology laboratory designed and validated waste-handling protocols with simulated patient trash to ensure adequate sterilization. The results of the validation process revealed that autoclave factory default settings are potentially ineffective for certain types of medical waste and highlighted the critical role of waste packaging in successful sterilization. The lessons learned from the JHH validation process can inform the design of waste management protocols to ensure effective treatment of highly infectious medical waste.

Analysis of defect generation in Ti–6Al–4V parts made using powder bed fusion additive manufacturing processes

Ti–6Al–4V parts made using additive manufacturing processes such as selective laser melting (SLM) and electron beam melting (EBM) are subject to the inclusion of defects. This study purposely fabricated Ti–6Al–4V samples with defects by varying process parameters from the factory default settings in both SLM and EBM systems. Process parameters are classified according to their tendency to create certain types of porosity. Finally, defect characteristics are discussed with respect to defect generation mechanisms; and effective process windows for SLM and EBM system are discussed.

Optimal Programming of Implantable Cardiac-Defibrillators

Implantable cardioverter-defibrillators (ICDs) reduce sudden cardiac death risk and improve survival in patients with a history of life-threatening arrhythmia or cardiac arrest (secondary prevention) and in high-risk patients without such a history (primary prevention).1–3 Patients with ICDs, however, may receive unnecessary shocks, which have been associated with proarrhythmia, anxiety, depression, poor quality of life, and possibly increased mortality.4–8 In contrast to drug therapy, in which a limited number of parameters (such as dose) are adjustable, hundreds of programmable parameters affect device therapy delivery. Moreover, selection of nonnominal parameter settings (ie, changing the out-of-the-box factory default settings) reduces morbidity and mortality compared with nominal settings in many clinical situations because of publication and regulatory delays.4,9,10 Thus, optimization of programming to prevent unnecessary shocks is paramount to minimize morbidity and mortality and is dependent on clinician proactivity. Delivery of ICD therapy for rhythms other than ventricular tachycardia (VT) or ventricular fibrillation (VF) is termed inappropriate therapy . It may result from inappropriate detection of supraventricular tachycardia (SVT) such as atrial fibrillation (AF) or sinus tachycardia or from oversensing of physiological (eg, T wave) or nonphysiological (eg, lead fracture noise) signals. Inappropriate shocks have been reported in 16% to 18% of ICD recipients and constitute 30% to 50% of all shocks.11–13 Although therapy delivered for a ventricular tachyarrhythmia is considered appropriate, a growing body of evidence has shown that programming antitachycardia pacing (ATP) or delaying shocks to permit nonsustained episodes to terminate significantly reduces the frequency of shock delivery. Koneru et al14 have used the term unnecessary shocks to refer to inappropriate shocks delivered for rhythms other than VT/VF and to include shocks delivered for VT that would have responded to ATP or terminated spontaneously if given time. Optimal programming minimizes unnecessary shocks. A …

P-002 Radiation exposure reduction in biplane fluoroscopic flat panel detectors

PurposeFollowing installation of a fluoroscopic digital flat panel detector (FPD) in the neuroangiography suite, three patients who underwent repeated angiographic studies for subarachnoid hemorrhage had complications with epilation, with one...

A Method for Optimizing and Validating Institution-Specific Flagging Criteria for Automated Cell Counters

Abstract Context.—Automated cell counters use alerts (flags) to indicate which differential white blood cell counts can be released directly from the instrument and which samples require labor-intensive slide reviews. The thresholds at which many of these flags are triggered can be adjusted by individual laboratories. Many users, however, use factory-default settings or adjust the thresholds through a process of trial and error. Objective.—To develop a systematic method, combining statistical analysis and clinical judgment, to optimize the flagging thresholds on automated cell counters. Design.—Data from 502 samples flagged by Sysmex XE-2100/5000 (Sysmex, Kobe, Japan) instruments, with at least 1 of 5 user-adjustable, white blood cell count flags, were used to change the flagging thresholds for maximal diagnostic effectiveness by optimizing the Youden index for each flag (the optimization set). The optimized thresholds were then validated with a second set of 378 samples (the validation set). Results.—Use...

A Method for Optimizing and Validating Institution-Specific Flagging Criteria for Automated Cell Counters

Automated cell counters use alerts (flags) to indicate which differential white blood cell counts can be released directly from the instrument and which samples require labor-intensive slide reviews. The thresholds at which many of these flags are triggered can be adjusted by individual laboratories. Many users, however, use factory-default settings or adjust the thresholds through a process of trial and error. To develop a systematic method, combining statistical analysis and clinical judgment, to optimize the flagging thresholds on automated cell counters. Data from 502 samples flagged by Sysmex XE-2100/5000 (Sysmex, Kobe, Japan) instruments, with at least 1 of 5 user-adjustable, white blood cell count flags, were used to change the flagging thresholds for maximal diagnostic effectiveness by optimizing the Youden index for each flag (the optimization set). The optimized thresholds were then validated with a second set of 378 samples (the validation set). Use of the new thresholds reduced the review rate caused by the 5 flags from 6.5% to 2.9% and improved the positive predictive value of the flagging system for any abnormality from 27% to 37%. This method can be used to optimize thresholds for flag alerts on automated cell counters of any type and to improve the overall positive predictive value of the flagging system at the expense of a reduction in the negative predictive value. A reduced manual review rate helps to focus resources on differential white blood cell counts that are of clinical significance and may improve turnaround time.

Minimum inspired oxygen concentration alarm

EDITOR: The use of anaesthetic machine and patient monitor alarms, in addition to clinical observation, can enhance patient safety, but it is very important that these limits are accurately set. The importance of these settings is highlighted by a critical incident which occurred recently in one of our theatres. Case report: An 8-yr-old, American Society of Anesthesiologists (ASA) I patient was scheduled for an elective ear, nose and throat procedure. Induction was uneventful and general anaesthesia was maintained with spontaneous ventilation via a laryngeal mask. The patient's head was draped and surgery commenced. An unobserved disconnection occurred at the junction of the circle-system breathing circuit tubing and the filter to which the gas analyser sampling line was attached (Fig. 1). The reduced movement of the reservoir bag was not initially noticed and the capnography trace continued as per normal. The inspired oxygen concentration decreased but the alarm did not sound as its setting had not been changed from the factory default of 18% for oxygen. Had it been set to above 21% it would have been activated. Fortunately the disconnection was discovered and the circuit reconnected before the patient sustained any harm.Figure 1.: Site of disconnection between circle breathing system and filter.The case prompted an audit at two hospitals in our region which demonstrated that the minimum inspired oxygen concentration alarm was changed from the factory reset by less than 10% of anaesthetists. Personal communication with a colleague from a neighbouring region revealed that two identical incidents had recently occurred in their hospital, and the same audit is at present being conducted in their hospital. Fortunately no patient suffered any harm as a result of the disconnections but the potential for patient awareness, movement, adverse airway events and hypoxia is evident. The use of an oxygen analyser is mandatory in accordance with the checklist for anaesthetic apparatus as set out by the Association of Anaesthetists of Great Britain and Ireland and is recommended in many other countries [1]. The Association guidelines however give no advice regarding the values to which the analyser's alarm limits should be set [2]. Oxygen concentrations are usually measured at either the fresh gas outlet or via the end-expired gas sampling line attached to, or near to, the filter. In addition to guarding against the delivery of hypoxic mixtures, the analyser (sampling end-tidal gases) can also help to detect problems with breathing circuit and ventilator integrity, and with alveolar hypoventilation [3,4]. A study by Knaack-Steinegger showed that disconnections were evident within 30 s using expired oxygen concentration alarms [5]. Disconnections are evident within a few breaths when using end-tidal gas monitoring with oxygen concentration alarms set to above 21%. Capnography alarms and the waveform are used by anaesthetists as a monitor for early detection of problems with patients' ventilation, including disconnections in the breathing system. In spontaneously breathing patients, where there is a disconnection proximal to the capnography sampling point, the capnography trace may well continue as per normal and hence this alarm would not detect the disconnection. An anaesthetic agent analyser is also useful to detect disconnections in a breathing system and guard against patient awareness, but factory default settings of 0% would need to be reset to minimum alveolar concentration (MAC) awake or above. The audit performed in our hospital also investigated the alarm settings of the agent analyser and found that in no theatres were the limits changed to above 0%. The oxygen alarms are often not set above 21% as doing so results in the alarm sounding when there is no (enriched) oxygen flowing through the circuit. This can be overcome by leaving the sampling line in continuity with the circuit and allowing a small quantity of oxygen to flow (most modern anaesthetic machines have a minimum oxygen flow preset). An alternate solution is to cap the circuit off at the end of the case. This also helps to prevent wastage of anaesthetic gases and stops the anaesthetic agent analyser alarm sounding (if set above 0%). Ventilator pressure alarms can detect leaks during mechanical ventilation, but they are not foolproof [6]. The minimum inspired oxygen alarm is a useful monitor but should be set above 21%, especially for spontaneously breathing patients and when the circuit is covered. Setting the anaesthetic agent alarm to above 0% further adds to patient safety. M. T. Dale D. Jadhav *Department of Anaesthesia, Critical Care and Pain Management, Leicester Royal Infirmary, Leicester, England

The strength-duration curve and its importance in pacing efficiency: a study of 325 pacing leads in 229 patients.

Pacemaker battery life is dependent on programmable parameters, principally pulse amplitude and pulse duration. High factory default settings cause excessive current drain. The strength-duration curve relates pacing threshold to pulse duration. The most energy efficient pacing occurs at chronaxie, a value of pulse duration derived from the curve. Strength-duration curves were calculated for 325 acutely implanted pacing leads. Chronaxie and rheobase were compared for atrial and ventricular leads. Chronaxie was compared with actual programmed pulse duration. There were 101 atrial and 224 ventricular leads, all passive fixation. The curve fit was good, (mean error +/- SD) 0.024 +/- 0.06 V for atrial curves and 0.008 +/- 0.034 V for ventricular curves. Mean (+/- SD) atrial and ventricular chronaxies were 0.24 +/- 0.07 ms and 0.25 +/- 0.07 ms, respectively. A "Z" value of 1.4 indicated that chronaxies might have been from the same population. Mean (+/- SD) atrial and ventricular rheobases were 0.51 +/- 0.2 V and 0.35 +/- 0.13 V, respectively. A "Z" value of 7.1 (P < 0.001) suggested atrial and ventricular rheobases were from differing populations. All patients had factory default pulse durations of 0.45 ms or 0.5 ms, exceeding acute chronaxie by a factor of two, thus, demonstrating suboptimal pacing. We conclude that understanding the strength-duration curve is critical. Sensible programming of other pacing functions optimizes longevity. Battery drain is reduced by programming pulse duration to chronaxie with a doubling of voltage threshold at this point to achieve a safety margin. Further study of chronaxie drift with time is required.